Graduate School of Environmental Science, Hokkaido University, Sapporo, 060-0810, Japan.
Department of Environmental Sciences, Jahangirnagar University, Dhaka, 1342, Bangladesh.
Ecotoxicol Environ Saf. 2020 Sep 1;200:110756. doi: 10.1016/j.ecoenv.2020.110756. Epub 2020 May 25.
Arsenic is a recognized highly toxic contaminant, responsible for numerous human diseases and affecting many millions of people in different parts of the world. Contrarily, curcumin is a natural dietary polyphenolic compound and the main active ingredient in turmeric. Recently it has drawn great attention due to its diverse biological activities, strong antioxidant properties and therapeutic potential against many human ailments. In this study, we aimed to explore the protective effects and the regulatory role of curcumin on arsenic-induced toxicity and gain insights into biomolecular mechanism/s. Arsenic (10 μM) treatment in PC12 cells for 24 h induced cytotoxicity by decreasing cell viability and intracellular glutathione level and increasing lactate dehydrogenase activity and DNA fragmentation. In addition, arsenic caused apoptotic cell death in PC12 cells, which were confirmed from flow cytometry results. Moreover, arsenic (10 μM) treatment significantly down-regulated the inhibition factors of autophagy/apoptosis; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap protein expressions, up-regulated the enhanced factors of autophagy/apoptosis; ULK, LC3, p53, Bax, cytochrome c, caspase 9, cleaved caspase 3 proteins and eventually caused autophagic and apoptotic cell death. However, curcumin (2.5 μM) pretreatment with arsenic (10 μM) effectively saves PC12 cells against arsenic-induced cytotoxicity through increasing cell viability, intracellular GSH level and boosting the antioxidant defense system, and limiting the LDH activity and DNA damage. Furthermore, pretreatment of curcumin with arsenic expressively alleviated arsenic-induced toxicity and cell death by reversing the expressions of proteins; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap, ULK, LC3, p53, Bax, cytochrome c, caspase 9 and cleaved caspase 3. Our findings indicated that curcumin showed antioxidant properties through the Nrf2 antioxidant signaling pathway and alleviates arsenic-triggered toxicity in PC12 cells by regulating autophagy/apoptosis.
砷是一种公认的剧毒污染物，导致许多人类疾病，并影响世界不同地区的数百万人。相比之下，姜黄素是一种天然的膳食多酚化合物，也是姜黄的主要活性成分。最近，由于其多种生物活性、强大的抗氧化特性以及对许多人类疾病的治疗潜力，它引起了极大的关注。在这项研究中，我们旨在探索姜黄素对砷诱导毒性的保护作用和调节作用，并深入了解生物分子机制。用 10 μM 砷处理 PC12 细胞 24 小时会通过降低细胞活力和细胞内谷胱甘肽水平、增加乳酸脱氢酶活性和 DNA 片段化来诱导细胞毒性。此外，砷会导致 PC12 细胞发生凋亡性细胞死亡，这从流式细胞术结果中得到了证实。此外，用 10 μM 砷处理会显著下调自噬/凋亡的抑制因子；mTOR、Akt、Nrf2、ERK1、Bcl-x、Xiap 蛋白表达，上调自噬/凋亡的增强因子；ULK、LC3、p53、Bax、细胞色素 c、caspase 9、cleaved caspase 3 蛋白，最终导致自噬和凋亡性细胞死亡。然而，姜黄素（2.5 μM）预处理与砷（10 μM）联合处理可有效挽救 PC12 细胞免受砷诱导的细胞毒性，增加细胞活力、细胞内 GSH 水平和增强抗氧化防御系统，同时限制 LDH 活性和 DNA 损伤。此外，用姜黄素预处理可显著减轻砷诱导的毒性和细胞死亡，通过逆转 mTOR、Akt、Nrf2、ERK1、Bcl-x、Xiap、ULK、LC3、p53、Bax、细胞色素 c、caspase 9 和 cleaved caspase 3 蛋白的表达。我们的研究结果表明，姜黄素通过 Nrf2 抗氧化信号通路表现出抗氧化特性，并通过调节自噬/凋亡来减轻 PC12 细胞中砷引起的毒性。
